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非巯基白蛋白作为帕金森病和 PARK2 病的氧化应激标志物。

Nonmercaptalbumin as an oxidative stress marker in Parkinson's and PARK2 disease.

机构信息

Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan.

Department of Neurosurgery, Faculty of Medicine, Juntendo University, Tokyo, Japan.

出版信息

Ann Clin Transl Neurol. 2020 Mar;7(3):307-317. doi: 10.1002/acn3.50990. Epub 2020 Feb 14.

Abstract

OBJECTIVE

To investigate the oxidized albumin ratio, which is the redox ratio of human nonmercaptalbumin (HNA) to serum albumin (%HNA), as a biomarker in idiopathic Parkinson's disease (iPD) and related neurodegenerative disorders.

METHODS

This prospective study enrolled 216 iPD patients, 15 patients with autosomal recessive familial PD due to parkin mutations (PARK2), 30 multiple system atrophy (MSA) patients, 32 progressive nuclear palsy (PSP) patients, and 143 healthy controls. HNA was analyzed using modified high-performance liquid chromatography and was evaluated alongside other parameters.

RESULTS

iPD and PARK2 patients had a higher %HNA than controls (iPD vs. controls: odds ratio (OR) 1.325, P < 0.001; PARK2 vs. controls: OR 1.712, P < 0.001). Even iPD patients at an early Hoehn & Yahr stage (I and II) showed a higher %HNA than controls. iPD patients had a higher %HNA than MSA and PSP patients (iPD vs. MSA: OR 1.249, P < 0.001, iPD vs. PSP: OR 1.288, P < 0.05). When discriminating iPD patients from controls, %HNA corrected by age achieved an AUC of 0.750; when discriminating iPD patients from MSA and PSP patients, an AUC of 0.747 was achieved. Furthermore, uric acid, an antioxidant compound, was decreased in iPD patients, similar to the change in %HNA.

INTERPRETATION

%HNA was significantly increased in iPD and PARK2 patients compared with controls, regardless of disease course and severity. Oxidative stress might be increased from the early stages of iPD and PARK2 and play an important role in their pathomechanisms.

摘要

目的

探讨氧化白蛋白比值(%HNA)作为特发性帕金森病(iPD)及相关神经退行性疾病的生物标志物。

方法

本前瞻性研究纳入 216 例 iPD 患者、15 例常染色体隐性遗传家族性 PD 患者(由 parkin 基因突变引起,即 PARK2)、30 例多系统萎缩(MSA)患者、32 例进行性核上性麻痹(PSP)患者和 143 例健康对照者。采用改良高效液相色谱法分析 HNA,并与其他参数一起进行评估。

结果

iPD 和 PARK2 患者的 %HNA 高于对照组(iPD 与对照组:比值比(OR)为 1.325,P<0.001;PARK2 与对照组:OR 为 1.712,P<0.001)。即使处于早期 Hoehn & Yahr 分期(I 期和 II 期)的 iPD 患者也表现出高于对照组的 %HNA。iPD 患者的 %HNA 高于 MSA 和 PSP 患者(iPD 与 MSA:OR 为 1.249,P<0.001;iPD 与 PSP:OR 为 1.288,P<0.05)。当以 %HNA 校正年龄来区分 iPD 患者与对照组时,曲线下面积(AUC)为 0.750;当以 %HNA 校正年龄来区分 iPD 患者与 MSA 和 PSP 患者时,AUC 为 0.747。此外,与 %HNA 变化相似,iPD 患者的抗氧化化合物尿酸降低。

结论

与对照组相比,iPD 和 PARK2 患者的 %HNA 显著增加,无论疾病过程和严重程度如何。氧化应激可能从 iPD 和 PARK2 的早期阶段开始增加,并在其发病机制中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b814/7086006/3ec1d477312c/ACN3-7-307-g001.jpg

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